Spherocytosis - An Overview

Created 7 October 2010.

Updated 1 August 2021 (added new case study)

Updated 7 January 2026 (updated to new format)

Here’s a real-life full blood count result; just one among dozens that I happened across as I do.

            HBM   WBCM    PLT    HCT   RBCM   MCVM   MCHM  MCHCM    RDW      N

310517      118  10.60    243  0.364   4.08   89.2   28.9    324   16.5   7.60

170817      125  14.80    309  0.387   4.37   88.6   28.6    323   17.5   9.30

031017      118  11.50    266  0.358   4.10   87.3   28.8    330   16.6   7.20

121218 F    125  18.08    342  0.367   4.27   85.9   29.3    341   16.3  12.09

              L      M      E      B   RET%   RETA    IRF    NUC     GF    ESR

310517     2.20   0.60   0.10   0.00    5.3 214.00    7.4                     

170817     4.20   0.90   0.30   0.10                                          

031017     3.10   0.90   0.30   0.10    8.2 336.00   12.2                   11

121218 F   4.44   1.12   0.33   0.10    7.2 309.10   14.1                   11

The blood count was normal in all respects.. but for the reticulocyte count. Lots of young red cells. Clearly in increase in red cell production. But a normal haemoglobin. What’s going on there?  A well-compensated haemolytic process was taking place.

 And then I looked down the microscope

The average red cell has a biconcave disc shape – you can tell this from the central pallor of the cell. Spherocytes lack this pallor – indeed the colour is darker towards the centre as these cells are thickest there.

Biconcave cells are flexible. Rather akin to a floppy bag of water. A spherocyte is spherical and is not so flexible. Rather akin to a balloon.

Hereditary Spherocytosis arises from a malformation in the red cell membrane caused by ah hereditary defect in one (or more) of the constituents of the erythrocytic cytoskeleton. Proteins most commonly at fault are

· Spectrin

· Ankyrin

· Band 3

· Protein 4.2.

Because the cell skeleton is defective the red cell contracts to a sphere through surface tension. Though the spherocytes have a smaller surface area through which oxygen and carbon dioxide can be exchanged compared to “normal” red cells, they perform adequately. However due to the relative inflexibility of the cells they have a shortened lifespan.

 Hereditary spherocytosis has a range of presentations depending on the severity of the red cell problem ranging from a well-compensated condition which is little more than a microscopic curiosity through to full-blown ongoing anaemia.

It is also claimed by some sources that the Rh null phenomenon gives rise to spherocytosis (it says so on Wikipedia so it must be true!). Presumably the missing Rh antigens are in part responsible for the red cells shape.

Acquired Spherocytosis occurs when there has been loss of membrane from otherwise normal cells and the cells have therefore contracted to a spherical shape. This loss can be immune-mediated or actual physical loss, and is seen in:

·  Autoimmune hemolytic anemia

· Paroxysmal cold hemoglobinuria

· Acute and delayed haemolytic transfusion reactions

· Haemolytic diseases of the newborn (HDN)

· hypophosphatemia

· Bartonellosis

· Snake bite

· hypersplenism

· Burns

· D.I.C

Testing for Spherocytosis is generally confirmatory. After all, seeing spherocytes is somewhat definitive, isn’t it?

Confirmatory testing in cases of acquired spherocytosis generally isn’t performed. After all the spherocytosis will be resolved when the cause of the spherocytosis is resolved.

The supposedly Gold Standard test for hereditary spherocytosis (the osmotic fragility test) was once commonplace in the district general hospital. However the demands of ISO standards and the fact that up to twenty percent of cases with marked spherocytes have a normal osmotic fragility has lead to the rise of the use of flow cytometry for such determinations.

A Case Study

A patient reported for ante-natal clinic at which a blood count was performed. She proved to be a tad anaemic, and the analyser suspected nucleated red cells (which isn’t an uncommon thing for it to suspect in pregnancy). For these reasons a blood film was made, and spherocytes were seen.

OTHERWISE, WELL

DOB  29/09/1977 Sex F Pat No 666999        Source    ANC      Received  12:58

Address   SOMEWHERE IN EUROPE,            Clinician WHO            07/10/2010

Specimen No : AW203214B    (Haematology)           

07/10/2010 11:15  EDTA

  Haemoglobin               10.7           g/dl         (  11.0 to 15.0  ) Auth

  White Blood Cells         10.5           10^9/l       (     4 to 11    ) Auth

  Platelets                 414            10^9/l       (   150 to 400   ) Auth

  Red Blood Cells           3.55           10^12/l      (   3.8 to 4.8   ) Auth

  Haematocrit               0.320          ratio        (  0.36 to 0.46  ) Auth

  Mean Cell Volume          91.3           fl           (    80 to 100   ) Auth

  Mean Cell Haemoglobin     30.1           pg           (    27 to 32    ) Auth

  Mean Cell Haemoglobin Con 33.0           g/dl         (    32 to 36    ) Auth

  Neutrophils               7.7            10^9/l       (     2 to 7.5   ) Auth

  Lymphocytes               2.0            10^9/l       (   1.5 to 4     ) Auth

  Monocytes                 0.6            10^9/l       (   0.2 to 1     ) Auth

  Eosinophils               0.2            10^9/l       (  0.02 to 0.5   ) Auth

  Basophils                 0.0            10^9/l       (     0 to 0.1   ) Auth

  XE FLAG1                  Spherocytosis ++                               Auth

  XE FLAG2                  ^A blood film has been reviewed                Auth

                            Cursor Down for more

The patient’s (real) name rang a bell – I knew this patient had hereditary spherocytosis. This is a condition in which the patient’s red cell survival is decreased because of a problem with red cell membrane structure. Rather than being biconcave discs, the patient’s cells are spherical. Therefore not so flexible, and don’t live as long. Normally this condition is well compensated, but when the patient is unwell for other reasons, the HS can be aggravated and cause an anaemia.

Usually spherocytes are detected microscopically. In the case above a blood film was made because blood count parameters fell outside the reference range, and the automated analyser suspected nucleated red cells (which isn’t uncommon in pregnancy).

However I’m left wondering. Someone with HS having a blood count for any other reason may well have normal numerical results (it happens!), and with no blood film being made, the condition would go unnoticed. In fact the patient under consideration has had six previous blood counts over the last three years, none of which triggered the making of a blood film by the automation.

So we have a potential failing in the system. We are (potentially) not finding cases of hereditary spherocytosis. At first thought I was rather concerned, but then again, does this actually matter? Many cases of HS (and the related HE) are often not clinically significant. Some patients with these conditions can (and do) go their entire lives with absolutely no problems being generated by the well-compensated haemolytic process.

It was suggested that cases of HS have raised reticulocytes and so we could use that as a pointer, but performing reticulocyte counts on every blood count would get rather expensive and would slow the process down. In conversation with colleagues it was suggested that the spherocytic cells may well scatter light differently to biconcave discs, and that maybe one of the XE channels might find spherocytes. I relayed this suggestion to the analyser’s manufacturer who said not, but they were rather flummoxed by this problem. After some discussion we came to the conclusion that a case of HS which actually needs to be diagnosed will present either clinically with jaundice and/or anaemia, or will have an obvious problem with the blood count. And in 99.9% of the time will be suspected from a family history.

So there’s no need to change practice (at the moment…)

And here’s another one

P1234567            KIRK James T                 03.07.08  M   Specimen R,21.3133950.J   Clin dets Lower respiratory tract infection. . Collected 27.07.21 11:56     A.Diag PT         + 16.2         |Lymphs       1.28 APTT         31.7         |Monos      + 2.32 FIB        + 5.31         |Eosin        0.02 Hb         - 118          |Baso       + 0.13 WBC        + 30.82        |MPV          10.0 Plts         402          |PCT          0.40 Hct        - 0.325        |NRBC         0.02 RBC        - 3.77         | MCV          86.2         | MCH          31.3         | MCHC       + 363          | Neuts      + 27.07        |

“Lower respiratory tract infection”… well – that explains the neutropenia but look at the anisopoikilocytosis and anisochromia… and spherocytes (!!!)

It turns out that James T Kirk (not the real name!) had been diagnosed with hereditary spherocytosis when a baby, and has had two or three blood count for various reasons in the meantime. Each time kicking off the sort of excitement that I felt when thinking I’d uncovered a new case of hereditary spherocytosis…

Some More Expert Opinion…:

https://docs.google.com/document/d/1_78tWsypqD1ehDQiXn2c90IbIgF1eOfkFbGtNvj9aiE/edit?usp=sharing

https://en.wikipedia.org/wiki/Spherocytosis

https://www.sciencedirect.com/topics/medicine-and-dentistry/spherocytosis

https://www.ncbi.nlm.nih.gov/pubmed/27837594

http://adulldayatwork.blogspot.com/2010/10/october-7-2010-thursday-hereditary.html